multinucleated giant cells,
by specialized membrane
structure, clear zone, and
REGULATION OF RESORPTION
• Bone resorption involves highly coordinated
interaction between osteoblasts and
osteoclasts that are modulated by enzymes,
hormones,and RANK/RANKL/OPG system.
• Mature protein of 380 amino acids.
• Lacks transmembrane and cytoplasmic domains and
is secreted as a soluble protein.
• Osteoclast formation and activation is critically
regulated by the RANKL/RANK/OPG.
• The major biological action of OPG is inhibition of
osteoclast differentiation,resorptive function and
stimulation of osteoclast apoptosis.
• Clinical use of OPG as an anti-resorptive agent for
treating a variety of bone disorders characterized by
increased osteoclast activity.
• 616-amino acid peptide on the cell surface of
• Transforming growth factor-β (TGF-β) and vitamin
D3 (D3), increases RANK mRNA.
• Dexamethasone also enhances the mRNA
expression of RANK.
• 317-amino acid peptide produced by osteoblastic
lineage cells and activated T cells.
• When RANKL is expressed by cells of osteoblastic
lineage, it is cell-bound and when expressed by
T-lymphocytes it is known as soluble (s-RANKL).
• The role of RANKL, together with another very
important protein ligand, macrophage colony
stimulating factor (M-CSF) which binds to its
receptor c-forms, is to promote osteoclast
formation, fusion, differentiation, activation, an
d survival, thus favouring bone resorption.
• The biological effects of RANKL are produced
when it binds to RANK.
• Bone, bone marrow and lymphoid tissue including
fetal liver, lymph nodes, spleen and thymus express
high levels of mRNA for RANKL.
• Lower levels can be detected in heart, lung, thyroid,
• The soluble form of RANKL with M-CSF(macrophage
colony stimulating factor) induces osteoclast
formation even in the absence of cellular
• RANKL is produced by activated T cells as a
soluble protein, and therefore bone
resorption is regulated by the immune system,
where T-cell expression of RANKL may
contribute to pathological conditions such as
periodontitis and autoimmune arthritis.
• OPG is expressed by odontoblasts, ameloblasts,
and dental pulp cells.
• whereas RANK by odontoclasts, or by
• RANKL is expressed by odontoblasts, pulp,
periodontal ligament (PDL) fibroblasts, and
• As in osteoclasts, RANKL is also expressed in
odontoclasts, suggesting an autocrine or paracrine
effect of this regulator on these cells.
• The resorbing activity of odontoclasts is related
to the expression of the OPG/RANKL/RANK
system by PDL cells.
• It has been shown that PDL cells, isolated from
either non-resorbing deciduous teeth or
permanent teeth, express OPG, but not RANKL.
• In contrast, PDL cells derived from resorbing
deciduous teeth predominantly express RANKL
and less OPG.
• RANKL regulates odontoclast differentiation and
dose-dependently increases odontoclast
• OPG suppresses the RANKL-induced activation of
resorbing activity in odontoclasts.
• During permanent tooth eruption, cytotrophic factors
released from the dental follicle and/or the stellate
reticulum, such as parathyroid hormone-related
peptide (PTHrP), interleukin-1α, and TGF-β1, stimulate
the expression of RANKL.
• Out of these factors, PTHrP controls the regulation of
relative expression levels of RANKL/OPG on dental
follicle cells, as well as in human PDL cells.
• PTHrP increases RANKL and down regulates OPG
expression via a cyclic adenosine monophosphate
(cAMP)/protein kinase A (PKA) -independent
pathway, consequently leading to physiological root
resorption of deciduous teeth and successful eruption
of permanent teeth..
• The differentiation and activation of localized
preodontoclasts is also influenced by M-CSF. It
is expressed by odontoblasts, ameloblasts, and
dental pulp cells and its mechanism of action
appears to involve upregulation of RANK and
downregulation of OPG gene expression.
• Recent studies have suggested that the cells of
dental pulp may have some cytokine-producing
cells, which mediate monocyte-macrophage
lineage to form osteoclasts/odontoclasts
• T-cells can be activated to express RANKL, thereby inducing
differentiation and activation of preodontoclast cells under
the influence of locally produced cytokines.
• The odontoblasts and fibroblasts, which express RANKL,
interact with mononuclear progenitors and produce active
• Cytokines, IL-β, prostaglandin E2, TNF-α, or hormones such as
dexamethasone and 1, 25 dihydroxycolecalciferol (OH) 2 D3,
induced by the weakened PDL, stimulate expression of RANKL
by PDL fibroblasts, leading to the recruitment of active
odontoclasts and thus begin the resorption process.
• Recent studies, have corroborated that cementoblasts also
express RANKL and OPG, which is modulated by PTHrP.
• Cementoblasts secrete large quantities of OPG under
non-resorbing conditions, which could be the reason why
cementum is more protected than bone from resorption.
• Tartarate resistant acid phosphatase (TRAP) can
remove phosphate groups from osteopontin, an
event that subsequently disrupts adhesion of
osteoclasts to the bone.
• Intracellularly TRAP has been localized in the
transcytotic vesicles of osteoclasts(vesicles fuse
with transcytotic vesicles transporting matrix
• Root resorption is related to mechanical factors and
• During the dentinogenesis, the coronal dentin is
protected by the recently formed enamel, stellate
reticulum, stratum intermedium, and by the
• The root dentin is protected by Hertwig’s epithelial
root sheath, cementum, and after the
fragmentation of the sheath, by the cementoblasts
• In the case of dentin, osteoclasts are the primary
cells involved in root resorption.
• Knowledge on the mechanisms involved in
physiologic root resorption process may
enable us to delay or even inhibit exfoliation
of primary teeth in those cases where the
permanent teeth are not present.
• Development of therapeutic drugs.